Abstract and Introduction
Bone marrow fibrosis has recently been recognized as an adverse histological feature in patients with primary myelodysplastic syndromes. In this study, we assessed the prognostic impact of bone marrow fibrosis in patients with primary myelodysplastic syndromes under the recently revised new risk stratification systems: the New Comprehensive Cytogenetic Scoring System and the Revised International Prognostic Scoring System. From 2002 to 2012, a total of 79 (13%) patients with primary myelodysplastic syndromes and moderate/severe bone marrow fibrosis were identified; and these patients were compared with a control group of 166 patients with myelodysplastic syndromes but no significant fibrosis. Bone marrow fibrosis predicted an inferior overall survival and leukemia event-free survival for patients who received no hematopoietic stem cell transplant in univariate and multivariate analysis. Eleven patients with bone marrow fibrosis and 32 control group patients underwent hematopoietic stem cell transplant; and bone marrow fibrosis was an independent risk for an inferior overall survival but not leukemia-free survival. In addition, 17 (4%) patients developed bone marrow fibrosis during the course of myelodysplastic syndromes, which was accompanied by clinical and cytogenetic evidence of disease progression. JAK2 V617F mutations were detected in 6 of the 28 patients with bone marrow fibrosis presenting at the time of diagnosis and 2 of the 7 patients with bone marrow fibrosis developing in the course of disease, significantly higher than the control group patients. We conclude that bone marrow fibrosis is an adverse risk feature in primary myelodysplastic syndromes in the current therapeutic era, and this risk feature is not captured by newly revised risk stratification systems. Inclusion of bone marrow fibrosis in patient assessment may further aid in risk-adapted therapeutic decisions.
Bone marrow fibrosis is observed in approximately 10–20% of patients with primary myelodysplastic syndromes.[1,2] The clinical importance of bone marrow fibrosis in patients with myelodysplastic syndromes, however, has not been well recognized in the past and this histological feature was not incorporated into the 2008 World Health Organization classification system. In recent years, bone marrow fibrosis has been increasingly recognized as an adverse feature in patients with myelodysplastic syndromes, which correlates with increased risk of early bone marrow failure, transformation to acute myeloid leukemia, and an inferior patient outcome.[4–8] Some of these studies, however, preceded the European consensus criteria established for grading bone marrow fibrosis and/or prior to the recent advent of therapeutic agents for myelodysplastic syndromes, such as lenolidomide and hypomethylating agents. In a study conducted by Della Porta et al, patients with myelodysplastic syndromes who received hematopoietic stem cell transplantation or chemotherapy were censored at the time of therapeutic procedure. Therefore, the effect of bone marrow fibrosis in the current therapeutic paradigms is not clear. Furthermore, the molecular genetic features of these cases were not well described. Most importantly, the New Comprehensive Cytogenetic Scoring System for myelodysplastic syndromes and oligoblastic acute myeloid leukemia and the International Prognostic Scoring System-Revised have been published recently.[10,11] These systems have been shown to improve risk stratification for patients with primary myelodysplastic syndromes. It is unknown if bone marrow fibrosis remains to be a risk factor in myelodysplastic syndromes stratified according to these new systems.
In this study, we retrospectively analyzed the clinicopathological features of a large cohort of patients with myelodysplastic syndromes with bone marrow fibrosis. Many of our patients were treated with hypomethylating agents and a subset of patients was treated with hematopoietic stem cell transplant. The goals of this study were two-fold. First, to investigate the clinicopathological, cytogenetic, and molecular genetic features of myelodysplastic syndromes with bone marrow fibrosis; and second, to examine the prognostic impact of bone marrow fibrosis in patients treated using current treatment modalities and stratified according to the recently revised New Comprehensive Cytogenetic Scoring System and Revised International Prognostic Scoring System systems.
Mod Pathol. 2014;27(5):681-689. © 2014 Nature Publishing Group